Complementary recognition of alternative pathway activators by decay-accelerating factor and factor H.
The alternative complement pathway (ACP) functions as a surveillance mechanism by which microorganisms are opsonized with C3b in the absence of specific antibodies. The effectiveness of the ACP relies on its ability to distinguish self from non-self. This recognition function is mediated by C3 regulatory proteins including serum factor H, membrane cofactor protein (MCP), and membrane decay-accelerating factor (DAF). H activity against bound C3b can be increased by host components such as sialic acid and decreased by microbial polysaccharides. DAF and MCP may also recognize cell surface changes such as the presence of viral glycoproteins, since some virus-infected and tumor cells activate the ACP. In the present study, liposomes containing wild-type and mutant Salmonella minnesota lipopolysaccharide (LPS) were tested for ACP activation in serum. LPS-containing liposomes with bound C3b were then tested for their susceptibility to C3 convertase regulation by H and membrane DAF and for the sensitivity of their bound C3b to the cofactor activity of H. The results indicate that while the shortest mutant, Re595 LPS, did not induce ACP activation, R7 LPS containing an additional disaccharide did. This activation was poorly regulated by DAF but was inhibited by H. The regulatory activity of H for liposome-bound C3b, however, decreased when LPS of greater polysaccharide size was present in the membrane. In contrast the ACP activation induced by the phospholipid phosphatidylethanolamine was effectively inhibited by DAF but only poorly inhibited by H.
Kraus
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Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque 87131, USA.
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Mold
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D018958:CD55 Antigens / Q000494:pharmacology*; D017242:Complement Factor H / Q000494:pharmacology*; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology
D018958:CD55 Antigens; C493495:CFH protein, human; D008070:Lipopolysaccharides; D008081:Liposomes; D010743:Phospholipids; D017242:Complement Factor H